Cartridge for conducting a chemical reaction

• US 20050042137A1
• Filed: 09/29/2004
• Published: 02/24/2005
• Est. Priority Date: 05/28/1999
• Status: Active Grant

• Current Assignee: Cepheid (Danaher Corporation)
• Original Assignee: Cepheid (Danaher Corporation)
• Inventors: Chang, Ronald, Petersen, Kurt E., McMillan, William A., Pourahmadi, Farzad, Dority, Douglas B.
• Granted Patent: US 8,168,442 B2
• Time in Patent Office: Days
• US Class Current: 422/58
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0858 Side walls
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12Q 1/6844 Nucleic acid amplification reactions
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A cartridge for conducting a chemical reaction includes a body having at least one flow path formed therein. The cartridge also includes a reaction vessel extending from the body for holding a reaction mixture for chemical reaction and optical detection. The vessel comprises a rigid frame defining the side walls of a reaction chamber. The frame includes at least one channel connecting the flow path to the chamber. The vessel also includes flexible films or sheets attached to opposite sides of the rigid frame to form opposing major walls of the chamber. In addition, at least two of the side walls are optically transmissive and angularly offset from each to permit real-time optical detection of analyte in the reaction chamber.

Claims

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22. A device for conducting a chemical reaction, the device comprising:

a) a body having at least one flow path formed therein; and

b) a reaction vessel extending from the body, the vessel comprising;

i) a rigid frame defining side walls of a reaction chamber;

ii) at least one polymeric film attached to the rigid frame to form a major wall of the reaction chamber; and

iii) an inlet port for adding fluid to the reaction chamber;

wherein the inlet port of the vessel is connected to the at least one flow path in the body.

23. The device of claim 22, wherein the vessel includes first and second flexible sheets attached to opposite sides of the rigid frame to form two opposing major walls of the reaction chamber.

24. The device of claim 22, wherein the major wall is sufficiently flexible to conform to a thermal surface.

25. The device of claim 22, wherein at least two of the side walls are optically transmissive and angularly offset from each other by about 90°

.

26. The device of claim 22, wherein the ratio of the width of the chamber to the thickness of the chamber is at least 4:

1, and wherein the chamber has a thickness in the range of 0.5 to 2 mm.

27. The device of claim 22, wherein the body has formed therein:

i) a sample flow path;

ii) a separation region in the sample flow path for separating a desired analyte from a fluid sample; and

iii) an analyte flow path connecting the separation region to the inlet port of the vessel.

28. The device of claim 27, wherein the separation region in the body comprises:

a) a lysing chamber in the sample flow path for lysing cells or viruses in the sample to release material therefrom; and

b) at least one solid support positioned in the lysing chamber for capturing the cells or viruses to be lysed.

29. The device of claim 22, further comprising:

a) at least one thermal surface for contacting the major wall of the reaction chamber;

b) means for increasing the pressure in the reaction chamber, wherein the pressure increase in the chamber is sufficient to force the major wall to conform to the thermal surface; and

c) at least one thermal element for heating or cooling the surface to induce a temperature change within the chamber.

30. The device of claim 22, wherein at least two of the side walls of the reaction chamber are optically transmissive and angularly offset from each other, and wherein the device further comprises an optics system having at least one light source for transmitting light to the reaction chamber through a first one of the optically transmissive side walls and having at least one detector for detecting light emitted from the chamber through a second one of the optically transmissive side walls.

31. A method for conducting a chemical reaction, the method comprising the steps of:

a) introducing a sample into a device comprising;

i) a body having a sample flow path and having a separation region in the sample flow path for separating a desired analyte from the sample; and

ii) a reaction vessel extending from the body, the reaction vessel having a reaction chamber, an inlet port connected to the reaction chamber via an inlet channel, and an outlet port connected to the reaction chamber via an outlet channel;

wherein the body further has a first channel connected to the inlet port of the vessel and a second channel connected to the outlet port of the vessel;

b) separating the analyte from the sample in the separation region;

c) forcing the analyte to flow into the reaction chamber of the vessel via the first channel in the body while air displaced from the reaction chamber exits through the outlet channel and outlet port of the vessel into the second channel in the body; and

d) conducting a chemical reaction in the reaction chamber.

32. The method of claim 31, wherein the separation region comprises a lysing chamber in the sample flow path for lysing cells or viruses in the sample to release the analyte therefrom, and wherein the method further comprises the steps of:

i) capturing the cells or viruses with at least one solid support positioned in the lysing chamber; and

ii) lysing the cells or viruses in the lysing chamber.

33. The method of claim 31, wherein the vessel includes a plurality of walls defining the reaction chamber, at least one of the walls comprises a flexible sheet or film, the chemical reaction requires heating or cooling of the reaction chamber, and the reaction chamber is heated or cooled by:

i) placing the sheet or film in contact with at least one thermal surface;

ii) increasing the pressure in the reaction chamber, wherein the pressure increase in the chamber is sufficient to force the sheet or film to conform to the thermal surface; and

iii) heating or cooling the surface to induce a temperature change in the reaction chamber.

34. The method of claim 31, wherein the vessel includes a plurality of walls defining the reaction chamber, at least two of the walls are optically transmissive, and the method further comprises the steps of transmitting light to the reaction chamber through a first one of the optically transmissive walls and detecting light emitted from the chamber through a second one of the optically transmissive walls.

35. The method of claim 34, wherein the optically transmissive walls are angularly offset from each other by about 90°

.

36. The method of claim 31, further comprising the step of venting the air from the second channel in the body.

37. The method of claim 31, wherein the chemical reaction comprises nucleic acid amplification, and the method further comprises the step of mixing the analyte with amplification reagents prior to forcing the analyte to flow into the reaction chamber.